The overall objective of this proposal is to determine the capacity of human fetal pancreatic tissue to generate functional endocrine tissue in vitro and in vivo. These studies may provide important information relevant to diabetes and islet cell physiology. The specific aims are: 1. To study growth and development of human fetal islet cells and their precursors. a. Generation of islets or islet cell clusters (ICCs) and monolayers. b. Isolation of pure populations of islet cell precursors from ICCs and monolayers. (i) Cell sorting and beta-galactosidase (beta-gal) content. (ii) Infection with a retroviral vector containing the thymidine kinase (TK) gene. c. Expression of islet specific genes in whole pancreas, ICCs, and isolated islet cell populations. d. In vivo and in vitro functional studies using ICCs, monolayers and isolated islet cell populations. 2. To develop pancreatic beta-cell lines for studies of islet cell function in vitro and in vivo. a. Effects of the FGF family of growth factors on growth and differentiation of islet cells and their precursors. b. Development of an inducibly transformed pancreatic beta-cell line.